New FNIH Initiative Looks to Expedite Parkinson Disease Diagnosis Through Validated Biomarkers

Alessio Travaglia, PhD

Earlier this month, the Foundation for the National Institutes of Health (FNIH) announced a new public-private partnership that aims to clearly distinguish Parkinson disease (PD) from related neurodegenerative disorders, such as multiple system atrophy, Lewy body dementia, and progressive supranuclear palsy. This new initiative is comprised of the National Institute of Neurological Disorders and Stroke and the National Institute on Aging at the National Institutes of Health, the FDA, The Michael J. Fox Foundation for Parkinson’s Research, and stakeholders from the private sector, with a combined commitment of approximately $21 million.

Otherwise known as the Accelerating Medicines Partnership in Parkinson’s Disease and Related Disorders (AMP PDRD), this partnership builds on an earlier project, which consolidated data from various studies and increased the number of bio-samples for research to help advance the discovery and development of disease-modifying treatments for PD. AMP PDRD will look to identify and validate additional biomarkers, particularly those in more accessible tissues, that can accurately distinguish PD from other similarly-presenting disorders. The hope is that new biomarkers that assist in PD diagnosis at an early stage can enable appropriate treatment years before neurological disability.

Steve Hoffmann, MS

Following the announcement, Steve Hoffmann, MS, vice president in Research Partnerships and Director of the Biomarkers Consortium at the FNIH, and Alessio Travaglia, PhD, director of Translational Science, Neuroscience, at the FNIH, sat down to give an overview of the partnership. The duo described how it will leverage the available resources at hand, the challenges in differentiating PD from other neurodegenerative disorders, and the specific goals clinicians are hoping to achieve with the new partnership.

How does this new AMP PDRD leverage all the resources and expertise to further our understanding of PD biomarkers?

Steve Hoffmann, MS: Managed by the Foundation for the National Institutes of Health (FNIH), the Accelerating Medicines Partnership® (AMP®) in Parkinson’s Disease and Related Disorders (PDRD) is the latest public-private partnership in the AMP® portfolio. It brings together the scientific, technical, and financial expertise and resources from the National Institutes of Health, Food and Drug Administration, industry, academia, and advocacy organizations that also share the essential voice and experience of those living with Parkinson’s disease and related disorders. This collaborative alliance and combined resources promise to advance research more quickly and improve treatment options and outcomes for patients. Using cutting-edge technologies, novel tests for early disease diagnosis, and broad sharing of research data, AMP PDRD seeks to improve our understanding of Parkinson’s disease pathways, facilitate better selection of targets for drug development, and streamline processes for bringing new treatments to patients.

Are there certain emerging biomarkers we feel hold more promise and are worth more time and effort?

Alessio Travaglia, PhD: There's been significant discussion about moving toward a biological definition of Parkinson's disease and related biomarkers, a shift that would mark a substantial change in the field. A biological definition could lead to more precise diagnostics and targeted treatments, ultimately improving patient outcomes. While gaps remain in developing a consistent, quantitative, and less-invasive approach, alpha-synuclein seed amplification assays (SAA) are a groundbreaking development in Parkinson's disease biomarker research, offering a highly sensitive and specific method to detect misfolded alpha-synuclein aggregates. It is exciting that we can detect synuclein, a technique that holds promise for detecting disease earlier, monitoring progression, and evaluating therapeutic responses. Additionally, integrating measurements of Alzheimer's disease biomarkers alongside SAA could provide a comprehensive approach to neurodegenerative disease management, enhancing our ability to diagnose and treat Parkinson’s and other Parkinsonisms. This dual focus underscores the importance of advancing biomarker research to improve clinical outcomes across multiple neurodegenerative disorders.

What are some of the challenges with differentiating Parkinson disease from other related neurodegenerative disorders? On a molecular level.

Alessio Travaglia, PhD: Distinguishing Parkinson’s disease from other Parkinsonisms is extremely challenging. There is a high degree of heterogeneity in disease onset and progression - even within Parkinson’s - due to genetic, lifestyle, environmental, and other factors. This heterogeneity translates into the differences in pathophysiology between diseases and within various disease stages. This poses a significant challenge in selecting a single molecular target for drug discovery and reliably testing a drug in clinically, well-defined and biomarker-stratified patients, ensuring that the drug will most likely be beneficial. We currently lack the following: a disease mechanistic understanding to select impactful targets for drug discovery, biomarkers to prospectively identify and stratify patients most likely to respond to a given drug for the purpose of enrolling in trials, and – most importantly - a sensitive, objective biomarker that directly relates to clinical efficacy in terms of slowing or halting the disease. These are the goals of the Accelerating Medicines Partnership in Parkinson’s Disease and Related Disorders.

What is the value in conducting research at the earliest stages of PD? How do we get to this point?

Alessio Travaglia, PhD: We are now entering an era where disease-modifying therapies for neurodegeneration are on the horizon. Effective clinical trials require accurate diagnoses and recruitment of patients in the early stages of their disease, as treatments are more likely to be effective during this period. Biomarkers and genetic approaches, combined with clinical data, will be essential for accurately recruiting patients with Parkinson’s disease and related disorders. The AMP PDRD initiative will be instrumental in facilitating this process.

Are there specific goals of the AMP PDRD that these organizations would like to hit in the coming 5-10 years?

Steve Hoffmann, MS: The program aims to further establish the AMP PD Knowledge Portal as the central nexus of existing and new data generated from studies ofParkinson’s disease and related disorders using a harmonized protocol. The portal also will provide a powerful platform for data analysis along with tools to help all scientists visualize and interrogate complex datasets to identify key diagnostic biomarkers, progression, and therapeutic responses. Partner organizations and researchers hope to identify biomarkers that will differentiate Parkinson’s disease from other alpha synucleopathies and support the validation of more reliable and reproducible assays to detect these biomarkers.